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Nobel Prizes Recognize NIGMS Grantee, Research Areas

We learned this morning that Brian K. Kobilka of Stanford University School of Medicine, whose research is supported by NIGMS and other parts of NIH, will share the 2012 Nobel Prize in chemistry with Robert J. Lefkowitz of Duke University Medical School, a long-time grantee of the National Heart, Lung, and Blood Institute. They are being recognized “for studies of G-protein-coupled receptors.”

Their seminal work, primarily involving the β-adrenergic receptor, has widened understanding of how these biologically and medically important proteins operate. It has also contributed to an expanding library of related structures, which have been notoriously difficult to obtain. And it complements the ongoing efforts of many other researchers, including those funded through a variety of special NIH activities, among them the NIH Common Fund Structural Biology Program, which NIGMS helps administer.

Dr. Kobilka’s “molecular masterpiece,” the high-resolution structure of the β2-adrenergic receptor attached to its G protein partner, was published just last year. We’re proud that our funding contributed to this achievement.

We also congratulate the 2012 Nobel laureates in physiology or medicine, Sir John B. Gurdon of the Gurdon Institute and Shinya Yamanaka of Kyoto University and the Gladstone Institutes. They’re honored “for the discovery that mature cells can be reprogrammed to become pluripotent.” Their advances have propelled this area of stem cell research forward and have opened up many new avenues of investigation that are being pursued by NIGMS grantees.

We are delighted that these prizes, which were awarded during our 50th anniversary year, offer a further testament to the importance and value of basic research. We look forward to continuing to support basic studies that form the foundation for new and better ways to treat and prevent disease and improve health.

Dr. Kobilka has a long-standing grant from NINDS that supports structural and mechanistic studies on the adrenergic receptor. At a critical point in his structural studies, he received a high-risk, high-impact R21 award from the NIH Common Fund to pursue studies resulting in the stabilization of GPCRs.

As a longtime NIGMS grantee and grant reviewer, I read with interest your comments on Brian Kobilka and Robert Lefkowitz. I wanted to share my perspective.

NIH is often criticized for only funding “safe” research proposals. Whenever I hear that criticism, I point to Kobilka’s NIH grant GM083118-01A1, funded in 2008, which had as Aim 2 to “DETERMINE THE STRUCTURE OF THE β2AR-Gs COMPLEX.”

Solving a receptor/G protein complex structure was without precedent, but that aim was consistent with the stated goal of the NIH to support high-risk, high-impact structural biology on membrane proteins. This is the aim that won him the Nobel Prize, and NIH deserves much credit for its willingness to fund such a high risk project.

GPCRs represent the largest single class of targets for drug development. While much was known about the structure-activity relationships for ligands, receptors, and G proteins, virtually nothing was known about how these molecules functioned in concert. Kobilka’s work will truly transform our understanding of drug action, and represents the foundation of a new era (long-anticipated) of structure-based drug design.